Cell-to-cell variability in any molecular dimension from genome to metabolome is a hallmark of many cancers. Single-cell multi-omics tools provide a powerful technology to simultaneously resolve heterogeneity across multiple biomolecular layers and to discover new connectivity between the genome and its functional outputs. We are developing and deploying a suite of microchip-based tools for massively parallel analysis of the genome, transcriptome, functional proteins and metabolites at the single cell level. Examples include the integrated proteomic/metabolic single-cell chips for simultaneous quantification of functional proteins and small molecule metabolites in single cells as well as the droplet microfluidics-based toolkits for high-throughput simultaneous quantification of protein-DNA interactions, genome-wide expression, and functional proteins. In the meantime, we are developing computational frameworks that integrate high-dimensional data from different omics layers to derive systems-level understandings of the cause and consequence of tumor heterogeneity.

Integrated Proteomics/Metabolic Single Cell Barcode Chip (SCBC)

Flow-guided patterning of high-density ssDNA enables sandwich immunofluorescence-based microchip device for integrated profiling functional proteome and small molecule metabolites from single cells (commercialized by Isoplexis Corp). This first-in-the-field integrated proteomic/metabolic single-cell chip allows for the direct connection of cellular metabolic functions with their intracellular signaling events.

Transcriptome and Intracellular Proteomics via Sequencing (TIP-seq)

TIP-seq is a droplet microfluidics-based tool for simultaneous profiling of genome-wide expression and different types of functional proteins (cytokines, intracellular signaling phosphoproteins, surface receptors, etc.) in a large number of single cells. It can provide both an unbiased view of the whole transcriptome and critical phenotypical and functional readouts for each individual cell, allowing discovery-level analysis to be connected with and interpreted by relevant cellular phenotypes and functions.

PROtein-DNA Interactions and Gene Expression (PRODIGE)

PRODIGE is a droplet microfluidics-based high-throughput tool for joint quantification of histone modifications, TF bindings, and downstream genome-wide expression within the same single cells without the need of genetic manipulations. It can reveal how cell-to-cell heterogeneity in protein-DNA binding influences gene expression variability and decipher protein-mediated mechanisms that regulate cell-type-associated transcriptional programs in heterogeneous cell populations and under different developmental and/or disease conditions.

Spatial Omics and Metabolic function Analysis (SOMA)

SOMA enables simultaneous spatial profiling of major cellular bioenergetic activities, oxidative stress, and underlying transcriptome/proteome at near single-cell resolution in tissue sections. This technology  allows for dissecting intratumoral heterogeneity at both molecular and metabolic function levels and their intricate interactions within the tumor microenvironment.